title: Distinct ATOH1 and Neurog3 requirements define tuft cells as a new secretory cell type in the intestinal epithelium.
abstract: The unique morphology of tuft cells was first revealed by electron microscopy analyses in several endoderm-derived epithelia. Here, we explore the relationship of these cells with the other cell types of the intestinal epithelium and describe the first marker signature allowing their unambiguous identification. We demonstrate that although mature tuft cells express DCLK1, a putative marker of quiescent stem cells, they are post-mitotic, short lived, derive from Lgr5-expressing epithelial stem cells, and are found in mouse and human tumors. We show that whereas the ATOH1/MATH1 transcription factor is essential for their differentiation, Neurog3, SOX9, GFI1, and SPDEF are dispensable, which distinguishes these cells from enteroendocrine, Paneth, and goblet cells, and raises from three to four the number of secretory cell types in the intestinal epithelium. Moreover, we show that tuft cells are the main source of endogenous intestinal opioids and are the only epithelial cells that express cyclooxygenase enzymes, suggesting important roles for these cells in the intestinal epithelium physiopathology.
authors.affiliation: CNRS UMR5203, Montpellier F-34094, France.
authors.forename: François
authors.initials: F
authors.lastname: Gerbe
authors.forename: Johan H
authors.initials: JH
authors.lastname: van Es
authors.forename: Leila
authors.initials: L
authors.lastname: Makrini
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Brulin
authors.forename: Georg
authors.initials: G
authors.lastname: Mellitzer
authors.forename: Sylvie
authors.initials: S
authors.lastname: Robine
authors.forename: Béatrice
authors.initials: B
authors.lastname: Romagnolo
authors.forename: Noah F
authors.initials: NF
authors.lastname: Shroyer
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Bourgaux
authors.forename: Christine
authors.initials: C
authors.lastname: Pignodel
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
authors.forename: Philippe
authors.initials: P
authors.lastname: Jay
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000236:Adenoma / Q000378:metabolism / Q000473:pathology; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002454:Cell Differentiation; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D000089742:Doublecortin-Like Kinases; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology* / Q000378:metabolism; D007414:Intestinal Neoplasms / Q000378:metabolism / Q000473:pathology; D007420:Intestine, Large / Q000166:cytology / Q000378:metabolism; D007421:Intestine, Small / Q000166:cytology / Q000378:metabolism; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D055758:SOX9 Transcription Factor / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D000089742:Doublecortin-Like Kinases; D019746:Intramolecular Oxidoreductases; D007535:Isomerases; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D017346:Protein Serine-Threonine Kinases; D055758:SOX9 Transcription Factor; C500943:Atoh1 protein, mouse; C407737:Neurog3 protein, mouse; C527933:Sox9 protein, mouse; C077623:Ptgs2 protein, mouse; C496512:Ptgs1 protein, mouse; C485525:Dclk1 protein, mouse; C545516:HPGDS protein, mouse